Asthma has long been known to run in families. More recently, linkage studies have been conducted to identify specific genes involved. However, this work has gone slowly with multiple regions of linkage being identified. It is clear that gene-environment interactions are important in determining who develops asthma. Linkage studies conducted to date have not been designed to properly explore interactions. Given the complex nature of asthma, it is clear that candidate gene association studies will be necessary to identify disease genes and interactions with environmental factors.[unreadable] [unreadable] The role of air pollution in asthma exacerbation has long been appreciated. Ozone, an oxidant air pollutant, is one of the agents that can worsen existing asthma. Recent data suggest that ozone and other air pollutants may play a role in asthma etiology, but there are few data. Recent linkage studies in animals are beginning to identify genes that are involved in specific physiologic responses to ozone and other inhaled pollutants. [unreadable] [unreadable] This project includes several studies the role of genetic polymorphisms, environmental factors and their interaction in the etiology of childhood respiratory disease. The primary project is a family study of genetic susceptibility to asthma in a highly ozone exposed population, Mexico City. This study uses the case-parent triad design. We are actively conducting genetic analyses with these samples. [unreadable] [unreadable] I have established collaborations with two birth cohorts to study early life factors in the etiology of asthma. In the ALSPAC study birth cohort, we are examining the relation between breastfeeding and objective measures of atopy and asthma. I am also working Norwegian and other European asthma researchers to establish an asthma research program within the Norway Mother and Child Cohort (called MoBa), a population based cohort of 100,000 pregnant women in Norway who are being followed until their children reach adulthood. The asthma program will be focused around gene-environment interaction. NIEHS/DIR partially supports the MoBa study with the goal of enabling such add-on studies. As background for developing this project, I am analyzing data from the cohort to follow-up well established findings from the literature that children of later birth order are at decreased risk for asthma. This has been ascribed to greater childhood infections in later born children under the so-called "hygiene hypothesis". However, the in utero environment may also be different for later born children than for their older siblings. Because MoBa is one of the few studies including women who have enrolled for more than one pregnancy, I am examining whether exposures relevant to asthma risk in the offspring change from one pregnancy to the next and whether the atopic status of the mother changes across pregnancies. The other cohort that I have established collaboration with is ALSPAC, a birth cohort of 12,000 women in Avon, UK. We are examining the relation between breast feeding and the later development of asthma and atopy using objective measures of these phenotypes.